3-(difluoromethyl)-3-hydroxy-2-methylisoindolin-1-one | 1152033-18-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 3-(difluoromethyl)-3-hydroxy-2-methylisoindolin-1-one
• 英文别名: 3-(Difluoromethyl)-3-hydroxy-2-methylisoindol-1-one
• CAS: 1152033-18-5
• 化学式: C₁₀H₉F₂NO₂
• 分子量: 213.184
• InChiKey: GIUPEJGXGTUCAF-UHFFFAOYSA-N

物化性质

• 熔点：
  120-123 °C
• 沸点：
  371.4±42.0 °C(Predicted)
• 密度：
  1.407±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-(difluoro(phenylsulfanyl)methyl)-3-hydroxy-2-methyl-isoindolin-1-one 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲苯 为溶剂， 反应 5.0h， 以70%的产率得到3-(difluoromethyl)-3-hydroxy-2-methylisoindolin-1-one
  参考文献：
  名称：

  Fluoride-Catalyzed Addition of PhSCF₂SiMe₃ to N-Substituted Cyclic Imides Followed by Radical Cyclization: General Synthetic Strategy of gem-Difluoromethylenated 1-Azabicyclic Compounds

  摘要：

  PhSCF2SiMe3 (1) was found, for the first time, to undergo fluoride-catalyzed nucleophilic difluoro-(phenylsulfanyl)methylation reaction to cyclic imides 2, affording the corresponding adducts 3 in moderate to good yields. Reductive cleavage of the phenylsulfanyl group of N-alkylated adducts 3 with Bu3SnH/AIBN yielded gem-difluoromethylated products 4. Under the same reduction conditions, N-alkenylated and N-alkynylated adducts 3 afforded the corresponding gem-difluoromethylenated 1-azabicyclic compounds 5 and 6 with trans stereoselectivity. These compounds were employed as precursors for preparing substituted gem-difluoromethylenated pyrrolizidinones and indolizidinones 7 and 8 by treatment with Et3SiH/BF3 center dot OEt2, and compounds 9 and 10 by nucleophilic displacement of the hydroxyl group, using organosilanes in the presence of BF3 center dot OEt2. The synthesis of highly substituted gem-difluoromethylenated pyrrolizidines 13 and 14 was also demonstrated.

  DOI：

  10.1021/jo802794u

文献信息

• Bis(difluoromethyl)trimethylsilicate Anion: A Key Intermediate in Nucleophilic Difluoromethylation of Enolizable Ketones with Me₃SiCF₂H
  作者：Dingben Chen、Chuanfa Ni、Yanchuan Zhao、Xian Cai、Xinjin Li、Pan Xiao、Jinbo Hu

  DOI：10.1002/anie.201605280

  日期：2016.10.4

  A pentacoordinate bis(difluoromethyl)silicate anion, [Me3Si(CF2H)2]−, is observed for the first time by the activation of Me3SiCF2H with a nucleophilic alkali‐metal salt and 18‐crown‐6. Further study on its reactivity by tuning the countercation effect led to the discovery and development of an efficient, catalytic nucleophilic difluoromethylation of enolizable ketones with Me3SiCF2H by using a combination

  通过亲核碱金属盐和18-冠冕-6活化Me 3 SiCF 2 H首次观察到五配位双（二氟甲基）硅酸根阴离子[Me 3 Si（CF 2 H）2 ] -。通过调谐导致与我可烯醇化的酮的高效，催化亲核二氟甲基的发现和开发的抗衡作用在其反应性的进一步研究3 SICF 2通过使用CSF和18-冠-6作为引发体系的组合小时。机理研究表明，[（18-crown-6）Cs] + [Me 3 Si（CF 2 H）2 ]-是该催化反应的关键中间体。
• Fluoride-Catalyzed Addition of PhSCF₂SiMe₃ to <i>N</i>-Substituted Cyclic Imides Followed by Radical Cyclization: General Synthetic Strategy of <i>gem</i>-Difluoromethylenated 1-Azabicyclic Compounds
  作者：Teerawut Bootwicha、Duanghathai Panichakul、Chutima Kuhakarn、Samran Prabpai、Palangpon Kongsaeree、Patoomratana Tuchinda、Vichai Reutrakul、Manat Pohmakotr

  DOI：10.1021/jo802794u

  日期：2009.5.15

  PhSCF2SiMe3 (1) was found, for the first time, to undergo fluoride-catalyzed nucleophilic difluoro-(phenylsulfanyl)methylation reaction to cyclic imides 2, affording the corresponding adducts 3 in moderate to good yields. Reductive cleavage of the phenylsulfanyl group of N-alkylated adducts 3 with Bu3SnH/AIBN yielded gem-difluoromethylated products 4. Under the same reduction conditions, N-alkenylated and N-alkynylated adducts 3 afforded the corresponding gem-difluoromethylenated 1-azabicyclic compounds 5 and 6 with trans stereoselectivity. These compounds were employed as precursors for preparing substituted gem-difluoromethylenated pyrrolizidinones and indolizidinones 7 and 8 by treatment with Et3SiH/BF3 center dot OEt2, and compounds 9 and 10 by nucleophilic displacement of the hydroxyl group, using organosilanes in the presence of BF3 center dot OEt2. The synthesis of highly substituted gem-difluoromethylenated pyrrolizidines 13 and 14 was also demonstrated.